The reaction of 2-amino-N′-arylbenzamidines with tetracyanoethene reinvestigated: routes to imidazoles, quinazolines and quinolino[2′,3′:4,5]imidazo[1,2-c]quinazoline-8-carbonitrile

Article abstract of DOI:10.1016/j.tet.2015.09.049

2-Amino-N′-phenylbenzamidine (1a) reacts with tetracyanoethene (TCNE) to give 2-[2-(2-aminophenyl)-5-imino-1-phenyl-1H-imidazol-4(5H)-ylidene]malononitrile (11a), 4-(phenylamino)quinazoline-2-carbonitrile (5a) and 4-imino-3-phenyl-3,4-dihydroquinazoline-2-carbonitrile (9a). By optimizing the reaction conditions each of the compounds can be isolated as the main product and seven examples of these reactions are described. The [1H-imidazol-4(5H)-ylidene]malononitrile 11a was also independently synthesized in three steps from 2-amino-N′-(2-nitrophenyl)benzamidine (25) and TCNE in an overall yield of 56%. Dimroth rearrangement of either 2-aminophenyl- or 2-nitrophenyl-substituted [1H-imidazol-4(5H)-ylidene]malononitriles 11a or 27 with DBU in hot DCM gave the 2-[2-(2-aminophenyl)- and 2-[2-(2-nitrophenyl)-5-(phenylimino)-3H-imidazol-4(5H)-ylidene]malononitriles 28 (71%) and 34 (59%), respectively. Treatment of the [3H-imidazol-4(5H)-ylidene]malononitrile 28 with ethyl orthoformate in DMA at 165°C gave (Z)-2-[3-(phenylimino)imidazo[1,2-c]quinazolin-2(3H)-ylidene]malononitrile (36) (70%), thermolysis of which gave quinolino[3′,2′:4,5]imidazo[1,2-c]quinazoline-13-carbonitrile (30) (97%).

Full text of DOI:10.1016/j.tet.2015.09.049

Accepted Manuscript
The reaction of 2-amino-N'-arylbenzamidines with tetracyanoethene
reinvestigated: Routes to imidazoles, quinazolines and
quinolino[2',3':4,5]imidazo[1,2-c]quinazoline-8-carbonitrile
Styliana I. Mirallai, Maria Manoli, Panayiotis A. Koutentis
PII:
S0040-4020(15)30077-6
10.1016/j.tet.2015.09.049
TET 27146
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 22 July 2015
Revised Date: 9 September 2015
Accepted Date: 21 September 2015
Please cite this article as: Mirallai SI, Manoli M, Koutentis PA, The reaction of 2-amino-N'-
arylbenzamidines with tetracyanoethene reinvestigated: Routes to imidazoles, quinazolines and
quinolino[2',3':4,5]imidazo[1,2-c]quinazoline-8-carbonitrile, Tetrahedron (2015), doi: 10.1016/
j.tet.2015.09.049.
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ACCEPTED MANUSCRIPT
The reaction of 2-amino-N'-arylbenzamidines with tetracyanoethene
reinvestigated: Routes to imidazoles, quinazolines and
quinolino[2',3':4,5]imidazo[1,2-c]quinazoline-8-carbonitrile
Styliana I. Mirallai, Maria Manoli and Panayiotis A. Koutentis*
Department of Chemistry, University of Cyprus, P. O. Box 20537, 1678 Nicosia,
Cyprus, koutenti@ucy.ac.cy
2
-Amino-N'-phenylbenzamidine (1a) reacts with tetracyanoethene (TCNE) to give 2-
[
2-(2-aminophenyl)-5-imino-1-phenyl-1H-imidazol-4(5H)-ylidene]malononitrile
11a), 4-(phenylamino)quinazoline-2-carbonitrile (5a) and 4-imino-3-phenyl-3,4-
(
dihydroquinazoline-2-carbonitrile (9a). By optimizing the reaction conditions each of
the compounds can be isolated as the main product and seven examples of these
reactions are described. The [1H-imidazol-4(5H)-ylidene]malononitrile 11a was also
independently synthesized in three steps from 2-amino-N'-(2-nitrophenyl)benz-
amidine (25) and TCNE in an overall yield of 56%. Dimroth rearrangement of either
2
-aminophenyl- or 2-nitrophenyl-substituted [1H-imidazol-4(5H)-ylidene]malono-
nitriles 11a or 27 with DBU in hot DCM gave the 2-[2-(2-aminophenyl)- and 2-[2-(2-
nitrophenyl)-5-(phenylimino)-3H-imidazol-4(5H)-ylidene]malononitriles 28 (71%)
and 34 (59%), respectively. Treatment of the [3H-imidazol-4(5H)-ylidene]malono-
o
nitrile 28 with ethyl orthoformate in DMA at 165 C gave (Z)-2-[3-(phenylimino)-
imidazo[1,2-c]quinazolin-2(3H)-ylidene]malononitrile (36) (70%), thermolysis of
which gave quinolino[3',2':4,5]imidazo[1,2-c]quinazoline-13-carbonitrile (30) (97%).
Keywords: Heterocycles; quinazolines; imidazoles; tetracyanoethylene; amidines;
cyclization reactions.
1

ACCEPTED MANUSCRIPT
1
.
Introduction
2
-Amino-N'-arylbenzamidines 1, which exist in equilibrium with several proto- and
rota-tautomeric forms such as 2-amino-N-arylbenzamidine 1' (Scheme 1), are
synthetically useful building blocks and selected analogues target tyrosine kinases
1
which are important in cancer drug discovery and development. The benzamidines 1
can be readily prepared from: a) anthranilonitriles and anilines in the presence of
2
3
AlCl ; b) reduction of N-aryl-2-nitrobenzamidines using SnCl in concd. HCl; c)
3
2
4
reductive cleavage of 1,2,3-benzotriazines with hydrazine and Raney nickel; or from
d) HCl mediated hydrolytic cleavage of N-aryl-2,2-dimethyl-1,2-dihydroquinazolin-4-
1
b,1c
amines.
Scheme 1. Structures of 2-amino-N'-arylbenzamidine 1 (lowest energy conformer)
and the isomeric prototautomer 2-amino-N-arylbenzamidine 1' (next lowest energy
-1 5
conformer ∆E1-1' -2.7 kcal mol ).
2
-Amino-N'-arylbenzamidines 1 are particularly useful for the synthesis of
6
4
-(arylamino)quinazolines, a subclass of quinazolines, that also act as kinase
7
® 8
inhibitors. Several derivatives, e.g., Gefitnib (Iressa ), have been approved and
marketed for the treatment of cancer.
2

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Treatment of 2-amino-N'-arylbenzamidines 1 with formic acid gives the 4-(aryl-
9
amino)quinazolines 3. While reaction of 2-amino-N'-arylbenzamidines 1 with alkyl-
or aryl-aldehydes with or without iodine affords 2-(alkyl/aryl)-N-aryl-2,3-dihydro-
2
c,10
quinazolin-4(1H)-imines 2,
which can be oxidized to the aromatic 2-(alkyl/aryl)-4-
2
c,10
anilinoquinazolines 4.
-(arylamino)quinazoline-2-carbonitriles 5 as the sole products. Interestingly,
treating 2-amino-N'-phenylbenzamidine (1a) with phthalaldehyde afforded the poly-
Treating amidines 1 with tetracyanoethene (TCNE) gave
2
b
4
1
1
cyclic (Z)-N-phenylisoindolo[2,1-a]quinazolin-5(11H)-imine (6), while treatment
with tetracyanoquinodimethane (TCNQ) gave (Z)-2-{4-[4-(phenylimino)-3,4-
1
2
dihydroquinazolin-2(1H)-ylidene]cyclohexa-2,5-dien-1-ylidene}malononitrile (7); a
similar substitution of both geminal nitriles was also observed with 2-(1,3-dioxo-1,3-
1
3
dihydro-2H-inden-2-ylidene)malononitrile.
3

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Recently, we reported the reaction of 2-amino-N'-arylbenzamidines 1 with 4,5-
dichloro-1,2,3-dithiazolium chloride (8) (Appel salt) to give 3-aryl-4-imino-3,4-
1
4
dihydroquinazoline-2-carbonitriles 9 (Scheme 2). Since then, Szczepankiewicz et
15
al., developed a solvent free synthesis of 3-arylquinazolin-4(3H)-imines 10 from
-amino-N'-arylbenzamidines 1 and triethyl orthoformate (Scheme 2). The same
2
group also proposed the intermediacy of 3-arylquinazolin-4(3H)-imines in the
reaction of butane-2,3-diones with 2-amino-N'-arylbenzamidines to give 2-acetyl-3-
aryl-2-methyl-2,3-dihydroquinazolin-4(1H)-ones and suggested that the formation of
1
6
the quinazolin-4(3H)-imine was kinetically controlled.
Scheme 2. Reactions of 2-amino-N'-arylbenzamidines 1 with Appel salt 8 or triethyl
orthoformate to give 3-aryl-quinazolin-4(3H)-imines 9 and 10, respectively.
4

ACCEPTED MANUSCRIPT
The transformation of 2-amino-N'-arylbenzamidines 1 into quinazolin-4(3H)-imines is
important since this heterocycle features in biologically active compounds that behave
1
7
18
as cholinesterase inhibitors, cMET kinase inhibitors, modulators of chemokine
1
9
20
21
CCR3 activity, or exhibit antiproliferative or cardiotonic activities. An
understanding of the cyclization modes of 2-amino-N'-arylbenzamidines 1 can help
the development of improved syntheses of these and other heterocycles.
15,16
The recent results from the Szczepankiewicz team
prompted us to report our latest
study: a reinvestigation of the reaction of 2-amino-N'-phenylbenzamidine (1a) with
TCNE. In our hands, the reaction mixture was complex, affording not one but three
products that can be isolated by column chromatography (Scheme 3). Reaction
conditions were developed that enabled each of the compounds to be isolated as the
major product. The results support Szczepankiewicz’s kinetic ring closure
1
6
arguments. Finally, some cyclization chemistry of the obtained products are reported.
2
.
Results and discussion
2
.1.
Reinvestigating the reaction of TCNE and 2-amino-N'-phenyl-
benzamidine (1a)
2
b
In our hands, repeating the literature reaction, i.e. adding a solution of 2-amino-N'-
phenylbenzamidine (1a) (1 equiv) to a stirred solution of TCNE (2 equiv) in dry
o
EtOAc, at ca. 20 C failed after 5 h to give the expected precipitation of 4-(phenyl-
amino)quinazoline-2-carbonitrile (5a) in the reported 71% isolated yield. TLC
analysis of the reaction mixture supported the presence of three products that were
isolated by chromatography and identified as 2-[2-(2-aminophenyl)-5-imino-1-
phenyl-1H-imidazol-4(5H)-ylidene]malononitrile (11a) (12%), 4-(phenylamino)-
quinazoline-2-carbonitrile (5a) (37%) and 4-imino-3-phenyl-3,4-dihydroquinazoline-
5

ACCEPTED MANUSCRIPT
2
-carbonitrile (9a) (2%) (Scheme 3). The isolated yields of products 5a, 9a and 11a
were reproducible on both 0.1 and 1.0 mmol reaction scales and the possibility that
the products readily interconverted under the reaction conditions was excluded.
Scheme 3. The reaction of 2-amino-N'-phenylbenzamidine (1a) with TCNE according
to the reported procedure.
The structure of the 4,5-dihydroimidazole 11a was elucidated by single crystal X-ray
crystallography (Figure 1), while the structures of the quinazolines 5a and 9a were
supported by comparison of their known spectroscopic data. Nevertheless, owing to a
o
2b
mismatch in the reported melting point data of the quinazoline 5a (mp 84-85 C) and
o
that obtained from our sample (mp 211.5-212.5 C) we also solved its structure by
single crystal X-ray crystallography (Figure 2).
6

ACCEPTED MANUSCRIPT
Fig. 1. The crystal structure of 2-[2-(2-aminophenyl)-5-imino-1-phenyl-1H-imidazol-
4
(5H)-ylidene]malononitrile (11a) (50% probability ellipsoids and hydrogen atoms
…
…
omitted for clarity). An intramolecular N H-N hydrogen bond (N N 2.69 Å) holds
the 2-(2-aminophenyl) substituent in an almost coplanar conformation (18.8°) with
the imidazole ring.
Fig. 2. The crystal structure of 4-(phenylamino)quinazoline-2-carbonitrile (5a) (50%
probability ellipsoids and hydrogen atoms omitted for clarity).
7

ACCEPTED MANUSCRIPT
2
2
In light of our interest in the chemistry of benzamidines and TCNE we reoptimized
this reaction by examining the mode of addition, reagent equivalents, choice of
solvent, reaction temperature and use of acid or base additives.
Reversing the mode of addition, i.e. adding a solution of TCNE to a solution of
benzamidine 1a led to higher yields of the 4-(phenylamino)quinazoline 5a. To clarify
the need of excess TCNE we ran both modes of additions using equimolar ratios of
benzamidine 1a/TCNE (1:1) and obtained the products in very similar yields to the
respective reactions run with benzamidine 1a/TCNE ratio of 1:2. Investigating further,
we added EtOAc solutions of TCNE (1 equiv) to EtOAc solutions of the benzamidine
o
o
o
1
a (1 equiv) cooled to 0-5 C and also heated to 77 C. At 0-5 C the reaction after 3
days gave only two products, the quinazolines 5a and 9a in 92 and 1% yields,
o
respectively but at 77 C all three products formed and notably the yield of the
imidazole 11a was relatively high (25%). While the low temperature reaction gave a
surprisingly good yield of the phenylaminoquinazoline 5a (92%) it was difficult to
o
maintain the temperature of the reaction mixture at ca. 5 C for 3 days, as such, we
investigated the effect of additives (acids and bases) in the hope that these could
improve the reaction conditions or affect a change in the product distributions.
Regardless of the mode of addition, when a 1:1 ratio of benzamidine 1a to TCNE was
o
reacted in EtOAc at 20 C, the introduction of strong bases (0.25-1.5 equiv) such as
NaOH, DBU or i-Pr NEt led to very low product yields and predominantly formation
2
of intractable precipitates, while the addition of weaker bases such as pyridine or
NaOAc gave product distributions and yields similar to reactions that were run
without additives. The introduction of strong acids such as concd. HCl, TsOH·H O,
2
H SO and TFA, led to the formation of benzamidine salts, which precipitated from
2
4
the reaction mixture, and very little reaction was observed with the TCNE even after
8

ACCEPTED MANUSCRIPT
heating the reaction mixtures at reflux. The addition of milder acids, however,
significantly affected the yields and product distributions. When TCNE (1 equiv) was
added to a mixture of benzamidine 1a (1 equiv) and glacial acetic acid (AcOH) (pKa
o
4
.76) (0.5 to 2.0 equiv) in EtOAc at 20 C then the yields of the phenylamino-
quinazoline 5a improved; the highest yield (87%) was obtained using AcOH (1.5
equiv). Replacing AcOH with either formic acid (pK 3.77) or t-BuCO H (pK 5.02)
a
2
a
gave lower overall yields. Interestingly, when the mode of addition was reversed and
benzamidine 1a (1 equiv) was added to a mixture of TCNE (1 equiv) and AcOH (0.5-
1
.0 equiv) a very different product distribution was obtained, with the imidazole 11a
(32%) and the phenylaminoquinazoline 5a (33%) forming in near equal amounts. In
this case, replacing the AcOH with formic acid led to the imidazole 11a becoming the
major product (up to 43% using 0.5 equiv of HCO H), while products 5a and 9a were
2
observed as traces. The use of formic acid (0.5 equiv) to improve the yield of the
imidazole 11a was not applicable when the reaction solvent was replaced by THF,
DCM, acetone or acetonitrile (MeCN). Our best reaction conditions for preparing the
4
,5-dihydroimidazole 11a were when a solution of the benzamidine 1a (1 equiv) in
o
EtOAc was added dropwise to a hot (77 C) solution of TCNE (1 equiv) and formic
o
acid (0.5 equiv) in EtOAc followed by heating at 77 C for 2 h (Conditions A) which
gave the imidazole 11a in 45% yield. Using these conditions several analogues 11a-g
were prepared in 41-51% yields (Table 1, entries 1-7).
Since the addition of TCNE (1 equiv) to a mixture of benzamidine 1a (1 equiv) and
o
AcOH (1.5 equiv) in EtOAc at 20 C led to phenylaminoquinazoline 5a in 87% yield,
we then examined replacement of the solvent in the hope that this reaction could be
improved further. When the solvent was replaced by either THF, MeNO or DCM the
2
phenylaminoquinazoline 5a was isolated in good yields (64-80%) while in EtOH and
9

ACCEPTED MANUSCRIPT
PhH the yields were very low (8-17%). When MeCN used as the solvent the yield of
the phenylaminoquinazoline 5a (89%) was similar to that obtained with EtOAc (87%)
but, there was no trace of the imidazole 11a.
Table 1. Reactions of 2-amino-N'-arylbenzamidines 1 with TCNE under Conditions
a
A, B and C, respectively.
a
entry
Ar
conditions
yields 11 yields 5
yields 9a
(%)
(
%)
(%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
Ph
4-Tol
4-MeOC H
A
A
A
A
A
A
A
B
B
B
B
B
B
B
C
C
C
C
C
C
C
11a (45)
11b (41)
11c (48)
11d (51)
11e (43)
11f (42)
11h (44)
5a (6)
5b (6)
5c (7)
5d (6)
5e (7)
5f (5)
9a (trace)
9b (trace)
9c (trace)
9d (trace)
9e (trace)
9f (trace)
9g (trace)
9a (1)
9b (1)
9c (1)
9d (1)
9e (2)
6
4
4-FC H
6
4
4-ClC H
6
4
4-BrC H
6
4
3,4-(MeO) C H
5g (6)
2
6
3
3
3
Ph
4-Tol
4-MeOC H
0
0
0
0
0
0
0
0
0
0
0
0
0
0
5a (97)
5b (98)
5c (97)
5d (98)
5e (95)
5f (97)
5g (93)
5a (29)
5b (30)
5c (29)
5d (30)
5e (31)
5f (27)
5g (28)
1
1
1
1
1
1
1
1
1
1
2
2
6
4
4-FC H
6
4
4-ClC H
6
4
4-BrC H
9f (1)
9g (1)
6
4
3,4-(MeO) C H
2
6
Ph
4-Tol
4-MeOC H
9a (69)
9b (62)
9c (62)
9d (65)
9e (69)
9f (65)
9g (64)
6
4
4-FC H
6
4
4-ClC H
6
4
4-BrC H
6
4
3,4-(MeO) C H
2
6
a
Conditions A: a solution of the benzamidine 1 (1 equiv) in EtOAc was added dropwise to a hot (77
C) solution of TCNE (1 equiv) and formic acid (0.5 equiv) in EtOAc followed by heating at 77 C for
o
o
2
1
h; Conditions B: a solution of TCNE (1 equiv) in MeCN was added to a solution of the benzamidine
(1 equiv) and AcOH (1 equiv) in MeCN at 20 C and left to stir for 7-8 h; Conditions C: a solution
o
of the benzamidine 1 (1 equiv) in MeCN was added dropwise to a solution of TCNE (2 equiv) in
o
MeCN at -20 C and left to stir at this temperature for 1 d.
As such, the reaction in MeCN was investigated further and when the quantity of
AcOH added was reduced from 1.5 to 1 equiv the phenylaminoquinazoline 5a yield
improved to 97% and identified our best conditions (Conditions B) for the preparation
of the 4-arylaminoquinazolines 5. Interestingly, removal of the AcOH also led to high
yields (94%) of the quinazoline 5a but under these conditions the yields dropped for
benzamidine analogues that hosted electron withdrawing halogen substituents on the
aniline moiety. In these cases introducing the AcOH (1 equiv) additive to the reaction
mixtures helped return product yields to greater than 93% (Table 1, entries 8-14).
1
0

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During an initial screen of reaction temperature we also noted that lower reaction
o
temperatures (-20 C) led to higher yields of both the imidazole 11a (34%) and the
iminoquinazoline 9a (14%). A subsequent solvent screen identified that in DMF,
DCM, MeNO and MeCN no imidazole 11a formed and that in MeCN the yield of the
2
iminoquinazoline 9a reached 69%. In MeCN the equivalents of TCNE could be
reduced from 2 to 1 without a significant loss in product yield (69 to 64%) but these
reactions required at least 4 days to consume all the starting benzamidine 1a. Under
these partially optimized conditions reversing the mode of addition i.e. adding TCNE
o
(
1 equiv) to a -20 C cooled MeCN solution of the benzamidine 1a (1 equiv) led to a
~50/50 mixture of both quinazolines, but interestingly the same mode of addition
using EtOAc led to a good yield of the phenylaminoquinazoline 5a (77%) and only a
trace (1%) of the iminoquinazoline 9a. In light of the lengthy reaction times (4 days)
when a 1:1 ratio of reagents we chose our best conditions for the formation of the
o
iminoquinazoline 9a as the addition of the benzamidine 1a (1 equiv) to a -20 C
cooled MeCN solution of TCNE (2 equiv) (Conditions C). Using these conditions we
prepared several analogues 9a-g in 62-69% yields (Table 1, entries 15-21).
2
.2.
Mechanistic rationale for the formation of products 5, 9 and 11
2
.2.1. Formation of 4-arylaminoquinazoline-2-carbonitriles 5 and 3-aryl-4-imino-
,4-dihydroquinazoline-2-carbonitriles 9
3
2
-Amino-N'-phenylbenzamidine (1a) contains three different nitrogen atoms: the
primary amine of the aniline, which is the more nucleophilic, and two amidine
nitrogens which are more basic, preferentially protonating on the imine nitrogen
2
3
(
C=N-Ph) to give the more delocalized cation. Since primary anilines can react with
2
4
TCNE to give N-aryltricyanovinylamines in good yields, and in rare cases
1
1

ACCEPTED MANUSCRIPT
2
5
carbonimidoyl dicyanides, we assume that the reaction between the 2-amino-N'-
arylbenzamidines and TCNE yields an adduct 12 that converts to either the dicyanide
1
3 via loss of malononitrile (Path A) or the tricyanovinylamine 14 via loss of HCN
(Path B) both of which can exist in equilibrium with various proto- and rota-
tautomeric isomers (e.g., isomers, 13' and 14', respectively) (Scheme 4).
Scheme 4. Tentative formation of the dicyanide 13 and/or tricyanovinylamine 14.
Disappointingly, none of these possible intermediates were observed in the reaction
mixtures, presumably owing to a subsequent rapid intramolecular cyclization onto the
neighboring amidine moiety to give the observed quinazolines 5 and 9. There was
some tentative support, however, that the intermediate was the carbonimidoyl
dicyanide 13 rather than the tricyanovinylamine 14: Firstly, the initial TCNE adduct
1
2 was expected to have the aniline NH group H-bonded to the amidine enhancing its
acidity and therefore more likely to facilitate the subsequent elimination of
malononitrile; secondly, had the tricyanovinylamine 14 been the intermediate then
this could have reacted in a similar manner to TCNQ and led to the formation of the
1
2

ACCEPTED MANUSCRIPT
ylidenemalononitrile 15 (Scheme 5) (c.f. compound 7); thirdly, the carbonimidoyl
dicyanide 13 was expected to be the more reactive (electrophilic) of the two and thus
could explain why the subsequent cyclizations occurred so quickly that intermediates
were not isolable. The above suppositions are intuitively derived and a clear picture
can only come from further studies, nevertheless, for the purpose of the subsequent
discussions we assume the carbonimidoyl dicyanide 13 to be the intermediate.
Scheme 5. Possible cyclization products derivable from the tricyanovinylamine 14.
1
6
Computational studies by Szczepankiewicz et al., on the reaction of 2-amino-N'-
phenylbenzamidine (1a) with butane-2,3-dione suggested that in our case the 4-imino-
3
-phenylquinazoline 9a was the kinetic product and the phenylaminoquinazoline 5a
the thermodynamic product. Fortunately, when benzamidine 1a and TCNE reacted in
MeCN the relative formation of quinazolines 5a and 9a was satisfactorily controlled
by moderating the reaction temperature and mode of addition. In the absence of
additives the reaction mechanism presumably follows that shown in Scheme 6.
1
3

ACCEPTED MANUSCRIPT
Scheme 6. Unassisted intramolecular cyclizations of the possible dicyanide 13
intermediate to give the observed quinazolines 5a (thermodynamic product) and 9a
(kinetic product).
When preparing the arylaminoquinazolines 5, it was noted that electron withdrawing
halogens on the aniline moiety led to lower yields, necessitating the addition of AcOH
(1 equiv) to the benzamidine solution. We assume that the role of the weak acid is to
protonate the more basic amidine imine nitrogen (C=N-Ph) making it less
nucleophilic, to afford the intermediate 16 that then undergoes a subsequent
cyclization via the amidine amide-like nitrogen (=C-NH ) (Scheme 7).
2
1
4

ACCEPTED MANUSCRIPT
Scheme 7. Acid catalysed intramolecular cyclization of the possible dicyanide 13
intermediate to give the phenylaminoquinazoline 5a.
Worthy of note is that most of the reported cyclizations of 2-amino-N'-phenyl-
benzamidine (1a) that lead to the formation of 4-anilino or 4-arylimino quinazolines
have been performed with heating and thus the isolation in these cases of the
thermodynamic and not the kinetic product is unsurprising.
2
.2.2. Formation of 2-[2-(2-aminophenyl)-1-aryl-5-imino-1H-imidazol-4(5H)-ylid-
ene]malononitriles 11.
The mechanistic rationale for the formation of the red colored [1H-imidazol-4(5H)-
ylidene]malononitriles 11 was more complex. From our earlier work, we know that
2
-[2-aryl-5-imino-1-phenyl-1H-imidazol-4(5H)-ylidene]malononitriles 20 can be
2
2
prepared from the reaction of N'-arylbenzamidines 17 with TCNE. This addition of
26
TCNE to the amidine amide-like nitrogen (=C-NH ) (pK 8.2) was unexpected.
2
a
Presumably, the initial TCNE adducts 18 or 21 are in equilibrium but adduct 18
1
5

ACCEPTED MANUSCRIPT
proceeds more rapidly to the isolable tricyanovinylamidine 19 that then undergoes the
5
-exo dig cycloaddition to the observed imidazole 20 (Scheme 8).
Ar1
Ar2
Ar1
Ar2
Ar1
NH
N
N
CN
NC CN
N
fast
N
CN
CN
CN
CN
_
Ar2
HCN
N
N
H
H
2
CN
CN
Ar1
Ar2
18
19
20
N
TCNE
NH2
NC
NC
CN
CN
NC
Ar1
CN
CN
Ar1
CN
NH
1
7
Ar1
slow
HCN
N
N
N
_
CN
Ar2
N
Ar2
NH2
Ar2
NH
22
2
3
2
1
not observed
Scheme 8. The reaction of N'-arylbenzamidine 17 with TCNE to give 2-[2-aryl-5-
imino-1-phenyl-1H-imidazol-4(5H)-ylidene]malononitriles 20.
In the reaction between TCNE and 2-amino-N'-phenylbenzamidine (1a), which
contains a more nucleophilic phenylamine, the formation of the imidazole 11a was
surprising. Tentatively, the formic acid in the reaction mixture assists the formation of
the imidazole 11a in two distinct ways: firstly, by protonating the more basic amidine
imine nitrogen (C=N-Ph) which enables TCNE to react with the remaining amide-like
nitrogen (=C-NH ), and secondly, by facilitating an acid-catalyzed 5-exo dig
2
2
7
cycloaddition (Scheme 9).
1
6

ACCEPTED MANUSCRIPT
Scheme 9. Tentative reaction sequence for the conversion of the benzamidine 1a into
imidazole 11a via the tricyanovinylamidine intermediate 24.
Furthermore, this formic acid-catalyzed cyclization must be sufficiently fast to limit
the alternative cyclization involving the tricyanovinylamidine 24 to give again the
quinazoline 5a. Worthy of note was that a highly probable internal H-bond in the
tricyanovinylamidine 24 would hinder the latter cyclization. That the yield for the
imidazole 11a could not be improved above 45% suggests that the reaction is more
complex that we describe. At least half of the reaction products remain as intractable
polar materials and further work is needed to clarify the reactions mechanisms. We
o
note that 2-amino-N'-arylbenzamidines 1 in neat 85% formic acid heated at 95 C for
9
2
h afford the 4-arylaminoquinazolines 3 in 70-92% yields, however, no trace of
these products were observed in the reaction with TCNE.
2
.3.
Independent synthesis and chemistry of 2-[2-(2-aminophenyl)-5-imino-1-
phenyl-1H-imidazol-4(5H)-ylidene]malononitrile (11a)
Previously, we reported an efficient route to [1H-imidazol-4(5H)-ylidene]malono-
2
2
nitriles 20 via the reaction of TCNE with N'-arylbenzamidines 17 (Scheme 8). In a
similar manner the [1H-imidazol-4-ylidene]malononitrile 11a can be independently
1
7

ACCEPTED MANUSCRIPT
prepared by reacting TCNE with (Z)-2-nitro-N'-phenylbenzamidine (25) to give (Z)-2-
nitro-N'-phenyl-N-(1,2,2-tricyanovinyl)benzamidine (26) which on warming in MeCN
gave
2-[5-imino-2-(2-nitro-phenyl)-1-phenyl-1,5-dihydro-4H-imidazol-4-ylidene]-
malononitrile (27), mild reduction of which using Zn powder in AcOH gave the
desired (imidazolylidene)malononitrile 11a in four steps with a 43% overall yield
(Scheme 10).
Scheme 10. Independent synthesis of the [4H-imidazol-4-ylidene]malononitrile 11a.
Furthermore, [1H-imidazol-4(5H)-ylidene]malononitriles 20 can undergo a Dimroth
rearrangement in either DCM/DBU or in MeOH/NaOH to give 2-(2-phenyl-5-aryl-
3
,5-dihydro-4H-imidazol-4-ylidene)malononitriles, thermolysis of which afforded
2
2
imidazolo[4,5-b]quinolines. The analogous Dimroth rearrangement of the [4H-
imidazol-4-ylidene]malononitrile 11a, and subsequent thermolysis of the obtained
isomer 28, could give 2-(2-aminophenyl)-1H-imidazo[4,5-b]quinoline-9-carbonitrile
(
29), which on treatment with triethyl orthoformate should give either quinolino-
3',2':4,5]imidazo[1,2-c]quinazoline-13-carbonitrile (30) or quinolino[2',3':4,5]-
[
imidazo[1,2-c]quinazoline-8-carbonitrile (31) or both (Scheme 11).
1
8

ACCEPTED MANUSCRIPT
CN
CN
Dimroth
NC
rearrangement
NC
HN
H N
2
Thermolysis
N
NH
N
N
N
Ph
Ph
H N
2
11a
28
CN
N
N
N
3
0
1
CN
N
H N
2
N
N
N
(
EtO) CH
3
and / or
CN
N
H
N
N
29
3
N
Scheme 11. Proposed route to quinolino[3',2':4,5]imidazo[1,2-c]quinazoline-13-
carbonitrile (30) and quinolino[2',3':4,5]imidazo[1,2-c]quinazoline-8-carbonitrile (31).
Accessing either of these two pentacyclic heteroarenes looked attractive owing to
their potential biological and/or material properties. Interestingly the closely related
pyrido[3',2':4,5]imidazo[1,2-c]quinazoline (32) and pyrido[2',3'-4,5]imidazo[1,2-c]-
quinazoline (33) have been prepared by Maes using an altogether different transition
2
8
metal-catalyzed synthesis (Scheme 12).
1
9

ACCEPTED MANUSCRIPT
Scheme 12. Maes synthesis of pyrido[3',2':4,5]imidazo[1,2-c]quinazoline (32) and
2
8
pyrido[2',3'-4,5]imidazo[1,2-c]quinazoline (33).
o
As such, treating the 4,5-dihydroimidazole 11a with DBU (1 equiv) in DCM at 40 C
for 3 h gave the Dimroth rearrangement product 2-[2-(2-aminophenyl)-5-(phenyl-
imino)-3H-imidazol-4(5H)-ylidene]malononitrile (28) in 71% yield; interestingly, in
MeOH/NaOH the Dimroth reaction failed. Unfortunately, thermolysis of the
o
imidazole 28 in diphenyl ether at ca. 180 C led to a complex reaction mixture with no
major product (Scheme 13).
2
0

ACCEPTED MANUSCRIPT
Scheme 13. Dimroth rearrangement of the imidazoles 11a and 27 and attempted
thermal conversion to 1H-imidazo[4,5-b]quinoline-9-carbonitriles 29 and 35,
respectively.
In light of this, a semi-independent synthesis of the desired imidazo[4,5-b]quinoline
2
9 was attempted: the Dimroth rearrangement of the available 2-nitrophenyl-
substituted imidazole 27 using DBU/DCM gave the isomeric 2-nitrophenylimidazole
4 in 59% yield; similar to the amino analogue above, the attempted rearrangement in
3
MeOH/MeONa failed. Furthermore, the thermolysis of the 2-nitrophenylimidazole 34
o
in diphenyl ether at ca. 200 C time 48 h, led to a complex reaction mixture and
intractable solids. Any doubts regarding the structure of the 2-nitrophenyl Dimroth
product 34 was probed by reduction of the nitro group in the presence of Zn powder
(4 equiv) in AcOH, to give the amino analogue 28 in 57% yield identical to that
described above (Scheme 13).
To overcome the above, the [3H-imidazol-4(5H)-ylidene]malononitrile 28 was treated
o
with triethyl orthoformate in N,N-dimethylacetamide (DMA) at 165 C for 15 min to
give the orange colored (Z)-2-[3-(phenylimino)imidazo[1,2-c]quinazolin-2(3H)-ylid-
2
1

ACCEPTED MANUSCRIPT
ene]malononitrile (36) in 70% yield, the structure of which was supported by single
crystal X-ray crystallography (Figure 3). Differential scanning calorimetry (DSC)
studies of the imidazoquinazoline 36 indicated a decomposition onset point at
o
o
2
34.6 C and gratifyingly, heating the compound in diphenyl ether at 250 C for 20
min gave the desired quinolino[3',2':4,5]imidazo[1,2-c]quinazoline-13-carbonitrile
30) in 97% yield (Scheme 14).
(
Scheme 14. Synthesis of quinolino[3',2':4,5]imidazo[1,2-c]quinazoline-13-carbo-
nitrile (30).
Interestingly, attempts to prepare the other isomer, by treating the [1H-imidazol-
4
(5H)-ylidene]malononitrile (11a) with ethyl orthoformate gave two unexpected
products, the yellow colored 2-[(3-phenylquinazolin-4(3H)-ylidene)amino]ethene-
1
,1,2-tricarbonitrile (37) in 71% and the imidazo[1,2-c]quinazoline 36 (Scheme 15) in
6% yield. The structure of the tricarbonitrile 37 was supported by single crystal X-
1
ray crystallography (Figure 4).
2
2

ACCEPTED MANUSCRIPT
Scheme 15. Reaction of the [1H-imidazol-4(5H)-ylidene]malononitrile 11a with ethyl
orthoformate to give the ethene-1,1,2-tricarbonitrile 37 and the imidazo[1,2-c]-
quinazoline 36
2
-[(3-Phenylquinazolin-4(3H)-ylidene)amino]ethene-1,1,2-tricarbonitrile (37) showed
o
o
a decomposition with an onset temperature at 278.7 C and a peak max. at 300.4 C
(by DSC); however, 37 was thermally stable after heating in diphenyl ether at ca.
o
3
00 C for 24 h, indicating that it was not an intermediate to the formation of the
imidazoquinazoline 36. Presumably, under the reaction conditions the (imidazol-
ylidene)malononitrile 11a can ring open in two distinctly different ways, the first to
regenerate a tricyanovinyl intermediate (either before or after the quinazoline is
formed) that leads to the formation of the major product 37 and the second must be a
Dimroth related ring opening that leads to the formation of the minor product 36.
2
3

ACCEPTED MANUSCRIPT
Fig. 3. The crystal structure of (Z)-2-[3-(phenylimino)imidazo[1,2-c]quinazolin-
2
(3H)-ylidene]malononitrile (36) (50% probability ellipsoids and hydrogen atoms
omitted for clarity).
Fig. 4. The crystal structure of 2-[(3-phenylquinazolin-4(3H)-ylidene)amino]ethene-
1
,1,2-tricarbonitrile (37) (50% probability ellipsoids and hydrogen atoms omitted for
clarity).
2
4

ACCEPTED MANUSCRIPT
3
.
Conclusions
The reaction of 2-amino-N'-arylbenzamidines 1 and TCNE is more complex than
originally reported affording three products 5, 9 and 11 which, depending on the
reaction conditions can be isolated as the main reaction products. By adding the
benzamidines 1a-g to a hot EtOAc solution of TCNE in the presence of HCO H the
2
[
1H-imidazol-4(5H)-ylidene]malononitriles 11a-g can be prepared in 41-51% yields.
o
By adding TCNE to a solution of the benzamidines 1a-g and AcOH in MeCN at 20 C
the 4-(arylamino)quinazoline-2-carbonitriles 5a-g can be prepared in 93-98% yields.
o
While adding the benzamidines 1a-g to a cooled (-20 C) MeCN solution of TCNE
afforded the isomeric 3-aryl-4-iminoquinazoline-2-carbonitriles 9a-g in 62-69%
yields. Mechanistic rationale suggests that the latter quinazolines 9 are the kinetic
products and the 4-(arylamino)quinazolines 5 the thermodynamic products.
Furthermore, the use of mild acids such as AcOH and HCO H was beneficial in
2
enhancing the yields of the 4-(arylamino)quinazolines 5 and the [1H-imidazol-4(5H)-
ylidene]malononitriles 11. The imidazole 5a, which undergoes a Dimroth
rearrangement in the presence of DBU was also a useful precursor to a new
pentacyclic system quinolino[3',2':4,5]imidazo[1,2-c]quinazoline-13-carbonitrile (30).
The mechanistic rationale provided for the above transformations remains tentative
pending further studies, nevertheless we believe the chemistry demonstrates that 2-
amino-N'-arylbenzamidines 1 are valuable building blocks for heterocyclic synthesis
and warrant further study.
2
5

ACCEPTED MANUSCRIPT
4
4
.
Experimental Section
.1.
General procedures
Reactions were protected from atmospheric moisture by CaCl drying tubes.
2
Anhydrous Na SO was used for drying organic extracts and all volatiles were
2
4
removed under reduced pressure. All reaction mixtures and column eluents were
monitored by TLC using commercial glass backed thin layer chromatography (TLC)
plates (Merck Kieselgel 60 F ). The plates were observed under UV light at 254 and
2
54
2
9
3
65 nm. The technique of dry flash chromatography was used throughout for all
non-TLC scale chromatographic separations using Merck Silica Gel 60 (less than
.063 mm). Melting points were determined using a Koefler−Hotstage microscope
0
apparatus or a DSC with samples hermetically sealed in aluminum pans under an
o
argon atmosphere, using heating rates of 5 C/min. Solvents used for recrystallization
are indicated after the melting point. UV spectra were obtained using a Perkin-Elmer
Lambda-25 UV/vis spectrophotometer and inflections are identified by the
abbreviation “inf”. IR spectra were recorded on a Shimadzu FTIR-NIR Prestige-21
spectrometer with a Pike Miracle Ge ATR accessory and strong, medium and weak
1
13
peaks are represented by s, m and w, respectively. H and C NMR spectra were
recorded on a Bruker Avance 300 machine (at 300 and 75 MHz, respectively) or on a
5
00 machine (at 500 and 125 MHz, respectively). Deuterated solvents were used for
homonuclear lock, and the signals are referenced to the deuterated solvent peaks. APT
NMR studies identified quaternary, tertiary, secondary, and primary carbons, which
are indicated by (s), (d), (t), and (q) notations, respectively. Low resolution (EI) mass
spectra were recorded on a Shimadzu Q2010 GCMS with direct inlet probe. MALDI
TOF mass spectra were recorded on a Bruker Autoflex III Smartbeam instrument. 2-
2
6

ACCEPTED MANUSCRIPT
2
a
30
Amino-N'-aryl-benzamidines 1a-f and tetracyanoethylene (TCNE) were prepared
according to literature procedures.
4
.2.
Preparation of new 2-amino-N'-arylbenzamidines
4
.2.1. 2-Amino-N'-(3,4-dimethoxyphenyl)benzamidine (1g). To stirred anthranilo-
o
nitrile (550 µL, 5.36 mmol) at ca. 20 C was added in one portion powdered
anhydrous AlCl (706 mg, 5.36 mmol). The reaction mixture was then heated (ca. 100
3
o
C) until a homogenous melt formed. To this hot melt was then added 3,4-dimethoxy-
o
aniline (489 µL, 5.36 mmol) and the mixture was heated (ca. 100 C) for 12 h and
o
then allowed to cool to ca. 20 C. The resultant solid mass was then crushed and
slurried in 10% NaOH (40 mL), extracted with DCM (5 × 50 mL), washed with H O
2
(
1 × 40 mL) and the organic phase dried (Na SO ), adsorbed onto silica and
2 4
chromatographed (t-BuOMe/EtOH, 95:05) to give the title compound 1g (873 mg,
o
6
0%) as colorless needles, mp (hotstage) 144-145 C (c-hexane/DCM, 9:1); R 0.45 (t-
f
BuOMe/EtOH, 95:05); (found: C, 66.45; H, 6.45; N, 15.41. C H N O requires C,
15
17
3
2
6
6.40; H, 6.32; N, 15.49%); λmax(DCM)/nm 251 inf (log ε 4.20), 297 (3.91), 328
-1
(
3.91); νmax/cm 3493w, 3431w, 3366w and 3204w (NH ), 3007w (Ar CH), 2968w
2
and 2959w (Alk CH), 1626s, 1582m, 1574w, 1537w, 1504s, 1464w, 1451w, 1439w,
1
1
7
410w, 1375w, 1325w, 1279w, 1260w, 1231s, 1198m, 1161w, 1152w, 1132m,
026m, 941m, 868w, 842w, 818w, 773m, 762m, 748s, 719w; δ (500 MHz; CDCl )
H
3
.42 (1H, d, J 7.5, Ar H), 7.19 (1H, ddd, J 7.5, 7.5, 1.0, Ar H), 6.87 (1H, d, J 8.5, Ar
H), 6.74-6.68 (2H, m, Ar H), 6.58 (1H, d, J 2.0, Ar H), 6.54 (1H, dd, J 8.3, 2.3, Ar H),
.00 (2H, br s, NH ), 4.85 (2H, br s, NH ), 3.87 (3H, s, OCH ), 3.86 (3H, s, OCH );
6
2
2
3
3
δ (75 MHz; CDCl ) 156.6 (s), 149.9 (s), 147.8 (s), 145.1 (s), 142.1 (s), 131.1 (d),
C
3
2
7

ACCEPTED MANUSCRIPT
1
27.3 (d), 117.2 (d), 116.7 (d), 116.5 (s), 112.8 (d), 112.2 (d), 106.2 (d), 56.2 (q,
+
+
OCH ), 55.8 (q, OCH ); m/z (MALDI-TOF) 273 (MH +1, 5%), 272 (MH , 100).
3
3
4
.3.
The reaction of TCNE with 2-amino-N'-phenylbenzamidine (1a)
2
b
according to the reported literature
To a stirred solution of TCNE (256 mg, 2.00 mmol) in dry EtOAc (10 mL) at ca. 20
o
C was added a solution of 2-amino-N'-phenylbenzamidine (1a) (211 mg, 1.00 mmol)
o
in dry EtOAc (10 mL) and left to stir for 5 h at ca. 20 C. The reaction mixture was
then adsorbed onto silica and chromatographed (DCM/t-BuOMe, 90:05) to give 2-[2-
(2-aminophenyl)-5-imino-1-phenyl-1,5-dihydro-4H-imidazol-4-ylidene]malononitrile
o
(
11a) (38.2 mg, 12%) as red needles, mp (DSC) decomp. onset 197.9 C, peak max.
o
2
01.2 C (from n-pentane/THF, 90:10); R 0.47 (DCM/Et O, 98:02); (found: C, 69.20;
f
2
H, 3.72; N, 26.83. C H N requires C, 69.22; H, 3.87; N, 26.91%); λmax(DCM)/nm
1
8
12
6
2
56 inf (log ε 4.36), 296 inf (4.21), 336 (4.34), 407 (4.37), 431 (4.49), 510 (4.48);
-1
νmax/cm 3404w (NH ), 3327w, 3285w and 3231w (NH), 2226w and 2207w (C≡N),
2
1
1
8
7
622m, 1578w, 1551w, 1495s, 1477s, 1422s, 1396s, 1341m, 1318m, 1267m, 1248s,
229m, 1198w, 1169m, 1113w, 1077w, 1067w, 1026w, 989w, 943w, 877w, 847w,
33w, 812w, 785w, 774w, 744s, 721w; δ (500 MHz; DMSO-d ) 9.93 (1H, s, NH),
H
6
.75 (2H, br s, NH ), 7.61-7.59 (3H, m, Ar H), 7.40 (2H, d, J 6.5, Ar H), 7.18 (1H, dd,
2
J 7.8, 7.8, Ar H), 6.81 (1H, d, J 9.0, Ar H), 6.59 (1H, d, J 8.5, Ar H), 6.17 (1H, dd, J
8
1
1
.3, 8.3, Ar H); δ (125 MHz; DMSO-d ) one C (d) resonance missing, 169.1 (s),
C 6
66.7 (s), 155.2 (s), 154.5 (s), 135.6 (d), 134.0 (s), 130.7 (d), 130.1 (d), 128.8 (d),
17.7 (d), 115.0 (d), 114.3 (s, C≡N), 113.4 (s, C≡N), 104.2 (s), 63.2 [s, C(CN) ]; m/z
2
+
(
EI) 312 (M , 100%), 284 (7), 245 (8), 220 (11), 194 (22), 167 (8), 118 (35), 104 (22),
9
2 (14), 77 (46), 65 (10), 51 (18). Further elution (DCM/t-BuOMe, 90:20) gave
2
8

ACCEPTED MANUSCRIPT
4
-(phenylamino)quinazoline-2-carbonitrile (5a) (92.6 mg, 37%) as colorless needles,
o
o
mp (hotstage) 210-211 C (from CHCl ), mp (DSC) onset 211.7 C, peak max.
3
o
2b
o
2
7
12.5 C (lit. 84-85 C) (from CHCl ); R 0.58 (DCM/t-BuOMe, 95:05); (found: C,
3 f
3.29; H, 3.97; N, 22.60. C H N requires C, 73.16; H, 4.09; N, 22.75%);
15
10
4
-1
λmax(DCM)/nm 245 (log ε 3.66), 259 (4.75), 280 (3.28), 336 (4.27); νmax/cm 3402w,
3
373w and 3346w (NH), 3061w and 3011w (Ar CH), 2247w (C≡N), 1614m, 1607m,
1
1
1
8
568s, 1530m, 1522m, 1495s, 1487s, 1449m, 1422m, 1412m, 1369m, 1361m,
317m, 1304w, 1292w, 1258w, 1217w, 1175w, 1161w, 1125w, 1107w, 1094w,
078w, 1032w, 993w, 903w, 864w, 795w, 789w; δ (500 MHz; CDCl ) 7.99 (1H, d, J
H
3
.0, Ar H), 7.94 (1H, d, J 8.0, Ar H), 7.91 (1H, d, J 7.5, Ar H), 7.78 (2H, d, J 8.0, Ar
H), 7.73 (1H, dd, J 7.8, 7.8 Ar H), 7.63 (1H, br s, NH), 7.46 (2H, dd, J 8.0, 8.0, Ar H),
.24 (1H, dd, J 7.5, 7.5, Ar H); δ (500 MHz; DMSO-d ) 10.31 (1H, br s, NH), 8.62
7
H
6
(
1H, d, J 8.0, Ar H), 7.98 (1H, dd, J 8.0, 8.0, Ar H), 7.88 (1H, d, J 8.0, Ar H), 7.81
1H, ddd, J 7.8, 7.8, 1.0, Ar H), 7.75 (2H, d, J 7.3, Ar H), 7.46 (2H, dd, J 8.0, 8.0, Ar
(
H), 7.23 (1H, dd, J 7.5, 7.5, Ar H); δ (75 MHz; DMSO-d ) 158.5 (s), 149.0 (s), 140.1
C
6
(s), 138.1 (s), 134.5 (d), 129.1 (d), 128.8 (d), 128.2 (d), 125.2 (d), 123.45 (d), 123.4
+
+
(
d), 117.0 (s), 115.6 (s); m/z (EI) 246 (M , 42%), 245 (M -1, 100), 219 (2), 192 (4),
69 (8), 123 (6), 102 (10), 97 (7), 77 (14). Further elution (DCM/t-BuOMe, 90:20)
gave 4-imino-3-phenyl-3,4-dihydroquinazoline-2-carbonitrile (9a) (4.7 mg, 2%) as
1
o
14
o
colorless needles, mp (hotstage) 141-142 C (lit. 141-142 C) (from c-hexane), mp
o
o
(
DSC) onset 143.9 C, peak max. 146.2 C (from c-hexane); R 0.48 (DCM/t-BuOMe,
f
9
0:10); λmax(DCM)/nm 237 inf (log ε 4.25), 245 inf (4.18), 255 (4.13), 265 (4.19), 274
-1
(
4.11), 298 inf (3.77), 311 (3.94), 324 (3.99), 340 inf (3.85); νmax/cm 3341w, 3308w
(NH), 3071w (Ar CH), 2239w (C≡N), 1643m, 1605w, 1574w, 1560m, 1491w,
1
472w, 1462m, 1348m, 1302m, 1283m, 1227w, 1217w, 1167m, 1138m, 1030w,
2
9